Uğur ÖZKERİM, Sıla ÖKSÜZ, Seval AY
Eurasian Journal of Medical Investigation - 2026;10(1):46-53
Objectives: Although nivolumab is a standard second-line option for advanced non-small cell lung cancer (NSCLC), treatment benefit differs substantially across patients in routine clinical practice. Biomarkers that may help explain this heterogeneity remain limited. Immune-related adverse events (irAEs) have been suggested as a potential clinical correlate of immune activation; however, their prognostic significance in real-world settings remains uncertain. Methods: We retrospectively reviewed patients with NSCLC who received nivolumab as second-line therapy at a single institution between 2018 and 2024. Immune-related adverse events were identified through systematic evaluation of clinical records. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates and Cox regression models. Results: Among 230 patients, 78 (33.9%) developed at least one irAE during treatment. Dermatologic, endocrine, and pulmonary toxicities were the most frequently observed events. In univariable analyses, irAE occurrence was associated with longer PFS (5.8 vs. 3.2 months, p=0.003) and OS (13.7 vs. 8.4 months, p=0.001). However, after multivariable adjustment for clinical confounders, the association with overall survival did not retain statistical significance. Conclusion: In this real-world cohort, the development of irAEs was associated with improved survival outcomes in unadjusted analyses, although this relationship was attenuated after adjustment. These findings suggest that irAEs may represent a clinical correlate of immune activation rather than an independent prognostic factor.
